Keywords
How to Cite
Abstract
Pioglitazone (pio) has been used as an effective hypoglycemic drug in medicine, however, the effects and mechanisms of pio on lipid metabolic disorder are still largely unknown. To explore the effects of pio on serum and liver lipid level and antioxidant ability of mice with lipid metabolic disorder, KKAy mice were treated with piofor 12 weeks and their lipid and antioxidant indices were compared to those of KKAy mice without pio treatment. C57BL/6J mice were used as control animals. The results show that pio treatment reduces serum and liver TG, elevates serum HDL-C level, increases serum and liver SOD activity, attenuates serum MDA content, ameliorates liver steatosis, induces liver PPARγexpression and enhances AMPKα phosphorylation level. In conclusion, the results indicate that pio could regulate blood lipid level, reduce liver lipid deposition and enhance antioxidant capacity of mice with lipid metabolic disorder, which is possibly through increasing AMPKα phosphorylation.
References
Lu YX, Zhang Q, Li J, Sun YX, Wang LY, Cheng WM, et al. Antidiabetic effects of total flavonoids from Litsea Coreana leve on fat-fed, streptozotocin-induced type 2 diabetic rats. Am J Chin Med 2010; 38: 713-25. http://dx.doi.org/10.1142/S0192415X10008184
Marx N, Duez H, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res 2004; 94: 1168-78. http://dx.doi.org/10.1161/01.RES.0000127122.22685.0A
Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun 2006; 340: 291-5. http://dx.doi.org/10.1016/j.bbrc.2005.12.011
Lamontagne J, Pepin E, Peyot ML, Joly E, Ruderman NB, Poitout V, et al. Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic beta-cell at submaximal glucose concentrations. Endocrinology 2009; 150: 3465-74. http://dx.doi.org/10.1210/en.2008-1557
Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB. Pioglitazone treatment activates AMPactivated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun 2004; 314: 580-5. http://dx.doi.org/10.1016/j.bbrc.2003.12.120
Komar CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function--implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod Biol Endocrinol 2005; 3: 41. http://dx.doi.org/10.1186/1477-7827-3-41
Castle CK, Colca JR, Melchior GW. Lipoprotein profile characterization of the KKA(y) mouse, a rodent model of type II diabetes, before and after treatment with the insulinsensitizing agent pioglitazone. Arterioscler Thromb Vasc Biol 1993; 13: 302-9. http://dx.doi.org/10.1161/01.ATV.13.2.302
Saha AK, Kurowski TG, Colca JR, Ruderman NB. Lipid abnormalities in tissues of the KKAy mouse: effects of pioglitazone on malonyl-CoA and diacylglycerol. Am J Physiol 1994; 267: E95-101.
Moritoh Y, Takeuchi K, Asakawa T, Kataoka O, Odaka H. The dipeptidyl peptidase-4 inhibitor alogliptin in combination with pioglitazone improves glycemic control, lipid profiles, and increases pancreatic insulin content in ob/ob mice. Eur J Pharmacol 2009; 602: 448-54. http://dx.doi.org/10.1016/j.ejphar.2008.11.017
Asakawa M, Takano H, Nagai T, Uozumi H, Hasegawa H, Kubota N, et al. Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 2002; 105: 1240- 6. http://dx.doi.org/10.1161/hc1002.105225
Negro R, Dazzi D, Hassan H, Pezzarossa A. Pioglitazone reduces blood pressure in non-dipping diabetic patients. Minerva Endocrinol 2004; 29: 11-7.
Kawai T, Takei I, Oguma Y, Ohashi N, Tokui M, Oguchi S, et al. Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes. Metabolism 1999; 48: 1102-7. http://dx.doi.org/10.1016/S0026-0495(99)90122-1 146 Journal of Pharmacy and Nutrition Sciences, 2011 Vol. 1, No. 2 Chen et al.
Heikkinen S, Auwerx J, Argmann CA. PPARgamma in human and mouse physiology. Biochim Biophys Acta 2007; 1771: 999-1013.
Chistiakov DA, Potapov VA, Khodirev DS, Shamkhalova MS, Shestakova MV, Nosikov VV. The PPARgamma Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects. Diab Vasc Dis Res 2010; 7: 56-62. http://dx.doi.org/10.1177/1479164109347689
Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, et al. Structure of the intact PPAR-gamma-RXRnuclear receptor complex on DNA. Nature 2008; 456: 350-6. http://dx.doi.org/10.1038/nature07413
Ondracek CR, Rushing CN, Reese VC, Oropeza CE, McLachlan A. Peroxisome proliferator-activated receptor gamma Coactivator 1alpha and small heterodimer partner differentially regulate nuclear receptor-dependent hepatitis B virus biosynthesis. J Virol 2009; 83: 12535-44. http://dx.doi.org/10.1128/JVI.01623-09
Kageyama H, Hirano T, Okada K, Ebara T, Kageyama A, Murakami T, et al. Lipoprotein lipase mRNA in white adipose tissue but not in skeletal muscle is increased by pioglitazone through PPAR-gamma. Biochem Biophys Res Commun 2003; 305: 22-7. http://dx.doi.org/10.1016/S0006-291X(03)00663-6
Krag MB, Nielsen S, Guo Z, Pedersen SB, Schmitz O, Christiansen JS, et al. Peroxisome proliferator-activated receptor gamma agonism modifies the effects of growth hormone on lipolysis and insulin sensitivity. Clin Endocrinol 2008; 69: 452-61. http://dx.doi.org/10.1111/j.1365-2265.2008.03231.x
Kim JH, Lewin TM, Coleman RA. Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones. J Biol Chem 2001; 276: 24667-73. http://dx.doi.org/10.1074/jbc.M010793200
Sanyal AJ, Mofrad PS, Contos MJ, Sargeant C, Luketic VA, Sterling RK, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2004; 2: 1107-15. http://dx.doi.org/10.1016/S1542-3565(04)00457-4
Chen J, Li D, Zhang X, Mehta JL. Tumor necrosis factoralpha-induced apoptosis of human coronary artery endothelial cells: modulation by the peroxisome proliferatoractivated receptor-gamma ligand pioglitazone. J Cardiovasc Pharmacol Ther 2004; 9: 35-41. http://dx.doi.org/10.1177/107424840400900i106
El Midaoui A, Wu L, Wang R, de Champlain J. Modulation of cardiac and aortic peroxisome proliferator-activated receptorgamma expression by oxidative stress in chronically glucosefed rats. Am J Hypertens 2006; 19: 407-12. http://dx.doi.org/10.1016/j.amjhyper.2005.11.006
Han Y, Wang Q, Song P, Zhu Y, Zou MH. Redox regulation of the AMP-activated protein kinase. PLoS One 2010; 5: e15420. http://dx.doi.org/10.1371/journal.pone.0015420
Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, Yano M, et al. Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes 2006; 55: 120-7. http://dx.doi.org/10.2337/diabetes.55.01.06.db05-0943
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright (c) 2011 Liangru Ke , Wei Zhu, Wei Zhu, Xiang Feng , Xiang Feng , Zhiming Shan , Zhiming Shan , Niman Zhou , Niman Zhou , Liangru Ke , Sifan Chen , Zili Zhang , Zili Zhang , Xincai Xiao , Xincai Xiao , Yanshuang Sun , Yanshuang Sun , Qing Wei , Qing Wei , Sifan Chen